1. Field of the Invention
This invention is generally directed to a hydrate of N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-α]-pyrimidin-7-yl}phenyl)acetamide (“Compound No. 1”) and to processes related to the use thereof in the synthesis of a polymorphic form of Compound No. 1.
2. Description of the Related Art
Recently, a new class of agents has undergone development for the treatment of insomnia. These agents are non-benzodiazepine compounds, which bind selectively to a specific receptor subtype of the benzodiazepine receptor. This receptor selectivity is thought to be the mechanism by which these compounds are able to exert a robust hypnotic effect, while also demonstrating an improved safety profile relative to the non-selective, benzodiazepine class of agents. The first of these agents to be approved by the United States Food and Drug Administration (FDA) for marketing in the United States was Ambien® (zolpidem tartrate), which is based on the imidazopyridine backbone (see U.S. Pat. Nos. 4,382,938 and 4,460,592). In addition to Ambien®, another compound known as Sonata® (zaleplon), which is a pyrazolopyrimidine-based compound, has received FDA approval (see U.S. Pat. No. 4,626,538). Recently, the FDA approved Lunesta™ (see U.S. Pat. No. 6,444,673) as a prescription sleep aid. Other non-benzodiazepine compounds and/or methods for making or using the same have also been reported (see, e.g., U.S. Pat. Nos. 4,794,185, 4,808,594, 4,847,256, 5,714,607, 4,654,347 and 5,891,891).
While significant advances have been made in this field, there is still a need in the art for compounds that are effective as sedative or hypnotic agents generally, particularly in the context of treating insomnia. One such compound is N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-α]-pyrimidin-7-yl}phenyl)acetamide (Compound No. 1), which is also known by the generic name “Indiplon”. Compound No. 1 is disclosed in U.S. Pat. No. 6,399,621 and has the following chemical structure:

In addition, U.S. Pat. Nos. 6,472,528 and 6,485,746 are directed to the synthesis of Compound No. 1 and to a controlled release pharmaceutical composition containing Compound No. 1, respectively. Furthermore, U.S. Pat. Nos. 6,384,221 and 6,544,999 are directed to certain polymorphic forms of Compound No. 1 (i.e., Forms I and II), while U.S. Pat. No. 6,903,106 is directed to an additional polymorphic form (i.e., Form III) of Compound No. 1.
While Compound No. 1 has proven particularly promising for the treatment of insomnia, improvements related to the preparation of Compound No. 1 are still desired.